Upregulated expression of NMDA receptor in the paraventricular nucleus shortens ejaculation latency in rats with experimental autoimmune prostatitis

Estimated 30%-40% of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) suffer from premature ejaculation (PE), which is difficult to cure, but the mechanism is still unknown. Based on the results of our previous clinical studies and animal experiments, we propose that the glutamatergic system dysfunction in the paraventricular nucleus (PVN) may be involved.To test this hypothesis, we used experimental autoimmune prostatitis (EAP) rats to investigate the effects of CP/CPPS on ejaculation behavior through integrating copulatory behavior testing, neuroelectrophysiologic experiments, and molecular biology technologies.Histological examination of prostate tissue in EAP rats exhibited consistent pathological findings with that in CP/CPPS patients. Behavior testing showed that ejaculation latency (EL) of EAP rats significantly shortened compared with the controls (5.1 ± 1.8 vs 9.1 ± 2.4 min, P < .001). Sympathetic nervous system (SNS) activity testing revealed that EAP rats displayed significantly higher plasma norepinephrine (NE) level (1780 ± 493 vs 1421 ± 453 pg/mL, P = .043) and SNS sensitivity (67.8 ± 9.6 vs 44.6 ± 8.7%, P < .001). Immunohistochemical detection and Western blot analysis both displayed that NR1 subunit expression of N-methyl-D-aspartic acid (NMDA) receptors in the PVN of EAP rats was significantly upregulated (P = .007 and P < .001). Furthermore, the expression of NMDA NR1 subunit positively correlated both with SNS sensitivity (r = .917, P < .001) and prostatic inflammation scores (r = .964, P < .001).This study shows that EAP rats suffer from the same PE symptom as CP/CPPS patients. CP/CPPS-induced inflammatory-immune response can significantly upregulate the expression of NMDA receptors in the PVN, which shortening the EL by enhancing SNS sensitivity. However, the exact mechanism of chronic inflammation in the prostate causing the upregulated expression of NMDA receptors needs to be further studied.